Tuberculous lymphadenitis and adrenalitis with concomitant Addison′s disease: A need to diagnose and treat early

Extrapulmonary tuberculosis often proceeds with an indolent course until a substantially infected organ is destroyed. This fact creates a great diagnostic challenge for clinicians. We report a rare case of tuberculous lymphadenitis and bilateral tuberculous adrenalitis with concomitant Addison′s disease successfully treated with antitubercular drugs and steroid replacement

Genome-Wide Association Study on Adiponectin-Mediated Suppression of HDL-C Levels in Taiwanese Individuals Identifies Functional Haplotypes in CDH13

CDH13 encodes T-cadherin, which is expressed in the vasculature and cardiac myocytes and is the receptor for hexameric and high-molecular-weight adiponectin. The CDH13 region is the most pivotal locus associated with adiponectin level. Mediation analysis is a method to explore the effect of a third variable, it is assumed that the magnitude of the relationship between the independent and dependent variables will be reduced by statistical adjustment for a third variable. In addition, mediation can further occur in the case when the mediator acts as a pathway-suppressor variable that means a suppression effect may be suggested if the statistical removal of a mediation effect could increase the magnitude of the relationship between the independent and dependent variables. Here, we aimed to explore the suppression effect in a genome-wide association study, and investigate possible mechanisms that may link adiponectin to CDH13 variants and high-density lipoprotein cholesterol (HDL-C). Genome-wide association data for adiponectin and HDL-C were accessible for 2349 Taiwan-biobank participants. The mediation analysis was conducted with the CDH13 lead single nucleotide polymorphism (SNP) rs4783244. The cloned constructs of CDH13 haplotypes (GG and TT) identified from the rs4783244 G/T and rs12051272 G/T SNPs were transiently expressed in HEK293T cells and investigated using the luciferase reporter assay. Genome-wide association analysis showed that HDL-C is significantly associated with variants in CDH13 after adjusting for the adiponectin level. The lead SNP rs4783244 was significantly associated with lower adiponectin levels and exhibited a suppression effect on HDL-C when adiponectin was included as a third factor in the mediation analysis. Luciferase reporter assay results further demonstrated that the GG haplotype increased enhancer activity, whereas the haplotype TT significantly reduced the activity of this enhancer. We present the first evidence of the suppressive role of adiponectin in the genome-wide association between CDH13 and HDL-C. CDH13 may increase the HDL-C levels, and its expression is suppressed by adiponectin

Is Laparoendoscopic Single-Site Adrenalectomy a Feasible Alternative in Treating Aldosterone-Producing Adenoma?

Objective. To compare laparoendoscopic single-site (LESS) and conventional multiport adrenalectomy in patients with aldosterone-producing adenoma (APA). Material and Methods. We retrospectively reviewed patients who had been clinically confirmed with unilateral APA and who underwent LESS or multiport adrenalectomy between 2009 and 2014. Perioperative data were obtained for all patients. Blood pressure and the levels of serum aldosterone, renin, and potassium were checked periodically. Results. We identified 45 APA patients in the LESS group and 71 in the multiport group. The baseline characteristics were matched between two groups. All adrenalectomies were completed successfully, except one with laparoscopic conversion in the single-port group and one open conversion in the multiport group. After a mean follow-up around one year, there were no significant group differences in the improvement of hypertension, number of types of medication taken, and cure of hypokalemia after operation. Conclusions. Our study confirm that LESS adrenalectomy achieved similar clinical and functional outcomes as conventional multiport adrenalectomy for management of unilateral APA

Pleiotropic Associations of RARRES2 Gene Variants and Circulating Chemerin Levels: Potential Roles of Chemerin Involved in the Metabolic and Inflammation-Related Diseases

Chemerin, an adipokine and inflammatory mediator, is associated with metabolic, inflammation- and immune-mediated diseases. The genetic, clinical, and biomarker correlates of circulating chemerin levels have not been completely elucidated. We analyzed the determinants and correlates of retinoic acid receptor responder 2 (RARRES2; encoding chemerin) gene variants and chemerin levels in the Taiwanese population. In total, 612 individuals were recruited. Clinical and metabolic phenotypes, 13 inflammatory markers, 5 adipokines, and 6 single-nucleotide polymorphisms (SNPs) covering the RARRES2 region were analyzed. High chemerin levels and chemerin level tertiles were positively associated with multiple metabolic phenotypes and circulating inflammatory marker and adipokine levels and negatively associated with high-density lipoprotein cholesterol and adiponectin levels and estimated glomerular filtration rates (eGFRs). Genotype and haplotype analyses showed that RARRES2 SNPs were significantly associated with chemerin, fibrinogen, interleukin 6, and lipocalin 2 levels. Stepwise logistic regression analysis showed that C-reactive protein level, leptin level, triglyceride level, eGFR, rs3735167 genotypes, sex, and soluble P-selectin level were independently associated with chemerin levels. In conclusion, pleiotropic associations were noted between RARRES2 variants, circulating chemerin levels and multiple metabolic phenotypes and inflammatory marker levels. This study provides further evidence for the potential roles of chemerin in metabolic and inflammation-related diseases

LIPC variants as genetic determinants of adiposity status, visceral adiposity indicators, and triglyceride-glucose (TyG) index-related parameters mediated by serum triglyceride levels

Abstract Background Visceral adiposity indicators and the product of triglyceride and fasting plasma glucose (TyG) index-related parameters are effective surrogate markers for insulin resistance (IR) and are predictors of metabolic syndrome and diabetes mellitus. However, their genetic determinants have not been previously reported. Pleiotropic associations of LIPC variants have been observed in lipid profiles and atherosclerotic cardiovascular diseases. We aimed to investigate LIPC polymorphisms as the genetic determinants of adiposity status, visceral adiposity indicators and TyG index-related parameters. Methods A total of 592 participants from Taiwan were genotyped for three LIPC single nucleotide polymorphisms (SNPs). Results The LIPC SNPs rs2043085 and rs1532085 were significantly associated with body mass index (BMI), waist circumference (WC), lipid accumulation product, visceral adiposity index, and TyG index-related parameters [including the TyG index, TyG with adiposity status (TyG-BMI), and TyG-WC index], whereas the rs1800588 SNP was only significantly associated with the TyG index. The associations became nonsignificant after further adjustment for serum TG levels. No significant association was observed between any the studied LIPC SNPs and IR status. Conclusion Our data revealed a pleiotropic association between the LIPC variants and visceral adiposity indicators and TyG index-related parameters, which are mediated by serum TG levels

Laparoendoscopic single-site adrenalectomy in patients with primary hyperaldosteronism: A prospective study with long-term follow up

Laparoendoscopic single-site (LESS) adrenalectomy is a promising minimally invasive technique, however, the current evidence has not confirmed its long-term effectiveness in primary aldosteronism (PA). We conducted a study to analyze the long-term efficacy of LESS adrenalectomy in patients with PA. A total of 49 patients who had been clinically confirmed with PA who had an indication for unilateral adrenalectomy were included in this study. Perioperative data were obtained for all patients. Blood pressure and the levels of serum aldosterone, renin, and potassium were checked periodically. The median follow-up was 16.5 months. No intra- or early post-operative complication occurred. All LESS adrenalectomies were completed successfully, except one with laparoscopic conversion. Hypokalemia was resolved in all cases and no patient required potassium supplements after surgery. Post-operative cure of hypertension was achieved in 63% of our patients. Overall, 84% of our PA patients had clinical improvement in blood pressure control after surgery. Our long-term experience revealed that LESS adrenalectomy is a safe and effective approach, which demonstrated comparable long-term cure and improvement of hypertension to a conventional laparoscopic series in treating PA

Laparoendoscopic single-site adrenalectomy versus conventional laparoscopic surgery: a systematic review and meta-analysis of observational studies,”

Objective. To compare laparoendoscopic single-site (LESS) and conventional multiport adrenalectomy in patients with aldosteroneproducing adenoma (APA). Material and Methods. We retrospectively reviewed patients who had been clinically confirmed with unilateral APA and who underwent LESS or multiport adrenalectomy between 2009 and 2014. Perioperative data were obtained for all patients. Blood pressure and the levels of serum aldosterone, renin, and potassium were checked periodically. Results. We identified 45 APA patients in the LESS group and 71 in the multiport group. The baseline characteristics were matched between two groups. All adrenalectomies were completed successfully, except one with laparoscopic conversion in the single-port group and one open conversion in the multiport group. After a mean follow-up around one year, there were no significant group differences in the improvement of hypertension, number of types of medication taken, and cure of hypokalemia after operation. Conclusions. Our study confirm that LESS adrenalectomy achieved similar clinical and functional outcomes as conventional multiport adrenalectomy for management of unilateral APA

Pleiotropic Effects of APOB Variants on Lipid Profiles, Metabolic Syndrome, and the Risk of Diabetes Mellitus

Apolipoprotein B (ApoB) plays a crucial role in lipid and lipoprotein metabolism. The effects of APOB locus variants on lipid profiles, metabolic syndrome, and the risk of diabetes mellitus (DM) in Asian populations are unclear. We included 1478 Taiwan Biobank participants with whole-genome sequence (WGS) data and 115,088 TWB participants with Axiom genome-wide CHB array data and subjected them to genotype–phenotype analyses using APOB locus variants. Five APOB nonsynonymous mutations, including Asian-specific rs144467873 and rs13306194 variants, were selected from participants with the WGS data. Using a combination of regional association studies, a linkage disequilibrium map, and multivariate analysis, we revealed that the APOB locus variants rs144467873, rs13306194, and rs1367117 were independently associated with total, low-density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL) cholesterol levels; rs1318006 was associated with HDL cholesterol levels; rs13306194 and rs35131127 were associated with serum triglyceride levels; rs144467873, rs13306194, rs56213756, and rs679899 were associated with remnant cholesterol levels; and rs144467873 and rs4665709 were associated with metabolic syndrome. Mendelian randomization (MR) analyses conducted using weighted genetic risk scores from three or two LDL-cholesterol-level-associated APOB variants revealed significant association with prevalent DM (p = 0.0029 and 8.2 × 10−5, respectively), which became insignificant after adjustment for LDL-C levels. In conclusion, these results indicate that common and rare APOB variants are independently associated with various lipid levels and metabolic syndrome in Taiwanese individuals. MR analyses supported APOB variants associated with the risk of DM through their associations with LDL cholesterol levels